Assessing Methods for Assigning SNPs to Genes in Gene-Based Tests of Association Using Common Variants

Gene-based tests of association are frequently applied to common SNPs (MAF>5%) as an alternative to single-marker tests. In this analysis we conduct a variety of simulation studies applied to five popular gene-based tests investigating general trends related to their performance in realistic situations. In particular, we focus on the impact of non-causal SNPs and a variety of LD structures on the behavior of these tests. Ultimately, we find that non-causal SNPs can significantly impact the power of all gene-based tests. On average, we find that the “noise” from 6–12 non-causal SNPs will cancel out the “signal” of one causal SNP across five popular gene-based tests. Furthermore, we find complex and differing behavior of the methods in the presence of LD within and between non-causal and causal SNPs. Ultimately, better approaches for a priori prioritization of potentially causal SNPs (e.g., predicting functionality of non-synonymous SNPs), application of these methods to sequenced or fully imputed datasets, and limited use of window-based methods for assigning inter-genic SNPs to genes will improve power. However, significant power loss from non-causal SNPs may remain unless alternative statistical approaches robust to the inclusion of non-causal SNPs are developed.

A comparison of a distance education and locally based course in an urban university setting

The purpose of this research was to compare the academic performance and attitudes of students at the instructor-based site of a televised course and the distant site. An earlier pilot program indicated the need for certain technical and structural interventions at the distant site such as multiple "press-to-touch" microphones, a site-administrator and participative seating arrangements. At the beginning of the class, demographic data were collected from the students at both sites through a questionnaire and supplemented with information from students' records. Factors such as age, gender, ethnicity, marital status, number of children, current class status, major, work status and CLAST scores (achievement tests) were examined. There were no significant differences between the students at the sites except ethnicity and reading CLAST scores. The instructor-based site had a higher percentage of Hispanic students and the distant site had a larger percentage of Caucasian and Black Americans. The distant site scored significantly better on the reading section of the CLAST achievement test. An evaluation instrument was distributed to both sites, at the midpoint of the semester, measuring their attitude toward the organizational, technical, and pedagogical factors of the course. A second evaluation instrument, measuring similar factors, but more in-depth, was distributed to both sites near the end of the term. Nine students at the distant site were interviewed along with the site administrator to collect additional information.^ Course completion rates, dropout rates, pass rates and final grades of students at both sites were compared. There were no significant differences in academic performance between the students at both sites, however, there were significant differences in their attitudes. Those at the instructor-based site gave better ratings to most of items in the evaluation instruments. Problems at the distant site included audio and visual clarity, lack of available assistance, too much nonrelated talking, not enough opportunities to ask questions or to interact with the instructor during class. ^